Dasatinib Followed by Stem Cell Transplant in Treating Older Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

A Phase II Study of Dasatinib (Sprycel®) (NSC #732517) as Primary Therapy Followed by Transplantation for Adults >/= 18 Years With Newly Diagnosed Ph+ Acute Lymphoblastic Leukemia by CALGB, ECOG and SWOG

This phase II clinical trial studies how well dasatinib followed by stem cell transplant works in treating older patients with newly diagnosed acute lymphoblastic leukemia. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving chemotherapy before a stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Monoclonal antibodies, such as alemtuzumab, may interfere with the ability of cancer cells to grow and spread. Giving more than one drug (combination chemotherapy) and giving dasatinib together with chemotherapy may kill more cancer cells.

Study Overview

• Status: Completed
• Conditions: Acute Lymphoblastic Leukemia; Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Drug: Dasatinib; Drug: Cyclophosphamide; Drug: Mercaptopurine; Drug: Vincristine Sulfate; Biological: Pegfilgrastim; Drug: Dexamethasone; Drug: Leucovorin Calcium; Drug: Etoposide Phosphate; Biological: Filgrastim; Drug: Melphalan; Drug: Fludarabine Phosphate; Drug: Tacrolimus; Biological: Alemtuzumab; Drug: Methotrexate; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Autologous Hematopoietic Stem Cell Transplantation; Procedure: In Vitro-Treated Peripheral Blood Stem Cell Transplantation

Detailed Description

PRIMARY OBJECTIVES:

I. Estimate the disease-free survival (DFS) and overall survival (OS) profiles in newly diagnosed patients 18 years or older who have Philadelphia chromosome positive (Ph+) (BCR/(v-abl Abelson murine leukemia viral oncogene homolog [ABL]+) acute lymphoblastic leukemia (ALL) receiving sequential dasatinib followed by allogeneic or autologous hematopoietic cell transplant (HCT) or chemotherapy followed by dasatinib maintenance.

SECONDARY OBJECTIVES:

I. Compare the OS and DFS profiles for each of the three cohorts to those from similar populations from other studies.

II. Determine the ability of dasatinib to produce or maintain a BCR/ABL-negative status, as judged by quantitative-polymerase chain reaction (Q-PCR) following sequential dasatinib, chemotherapy, and HCT.

III. Determine the feasibility of collecting adequate peripheral blood stem cells for autologous HCT following dasatinib therapy and assess for residual Ph+ (BCR/ABL+) cells by Q-PCR.

IV. Study the safety and efficacy of autologous HCT following therapy with dasatinib.

V. Study the safety and efficacy of reduced-intensity preparatory regimen followed by an allogeneic HCT following induction therapy with dasatinib.

VI. Study the safety and efficacy of dasatinib maintenance administered after allogeneic or autologous HCT or chemotherapy.

VII. Correlate plasma and cerebrospinal fluid (CSF) levels of dasatinib when given orally during induction.

OUTLINE: As of 8/21/2014, no new patients may be enrolled on E3903.

REMISSION INDUCTION THERAPY (RIT): Patients receive dasatinib orally (PO) daily continuously and dexamethasone PO or intravenously (IV) on days 1-7.

EARLY INTENSIFICATION THERAPY: Patients with bone marrow =< 20% blasts are assigned to cohort A and patients with bone marrow > 20% blasts are assigned to cohort B.

COHORT A: Patients receive dasatinib and dexamethasone as in RIT.

COHORT B: Patients receive dasatinib and dexamethasone as in RIT, and vincristine sulfate IV and daunorubicin hydrochloride IV on days 1, 8, and 15. Patients who do NOT achieve a complete response (CR) or CR with incomplete hematologic recovery based on bone marrow continue on to second induction therapy; patients who achieve a hematologic and morphologic CR continue on to CNS prophylaxis therapy.

SECOND INDUCTION THERAPY: Patients receive dasatinib and dexamethasone as in RIT, cyclophosphamide IV on day 1, daunorubicin hydrochloride IV and vincristine sulfate IV on days 1 and 8, and filgrastim subcutaneously (SC) beginning on day 9 and continuing for >= 7 days or one dose of pegfilgrastim on day 9.

CNS PROPHYLAXIS THERAPY: Patients receive dasatinib PO daily continuously during CNS prophylaxis therapy; methotrexate intrathecally (IT), vincristine sulfate IV, and methotrexate IV over 3 hours on days 1, 15, and 29; methotrexate PO every 6 hours for a total of 4 doses each on days 1-2, 15-16, and 29-30; leucovorin calcium IV on days 2, 16, and 30; and leucovorin PO calcium every 6 hours for a total of 8 doses each on days 3-4, 17-18, and 31-32.

TRANSPLANTATION OR ALTERNATIVE CHEMOTHERAPY AND MAINTENANCE THERAPY: Patients aged 50-70 years with an HLA-matched related or unrelated donor are assigned to allogeneic transplantation, patients aged 50-70 years without an HLA-matched related or unrelated donor are assigned to autologous transplantation, and patients aged > 70 years or who are not transplantation candidates are assigned to alternative chemotherapy.

ALLOGENEIC TRANSPLANTATION: Patients receive fludarabine phosphate IV over 30 minutes and alemtuzumab IV over 30 minutes on days -7 through -3 and melphalan IV over 30 minutes on day -2. Patients undergo allogeneic peripheral blood stem cell transplantation (PBSCT) on day 0. Patients then receive filgrastim SC beginning on day 1 and continuing until count recovery and tacrolimus IV or PO beginning on day -2 and beginning to taper on day 100 (for matched related donors) or day 180 (for mismatched related or unrelated donors). Beginning on day 30, patients receive dasatinib PO daily as maintenance therapy. Treatment continues for >= 12 months in the absence of disease progression.

AUTOLOGOUS TRANSPLANTATION:

MOBILIZATION: Patients receive etoposide phosphate IV continuously on days 1-4, high-dose cytarabine IV over 2 hours every 12 hours for a total of 8 doses on days 1-4, and filgrastim SC once or twice daily beginning on day 14 and continuing until peripheral blood stem cell collection is complete or WBC > 50,000/μL.

LEUKAPHERESIS: Patients undergo leukapheresis beginning when WBC > 10,000/μL for a target collection of >= 5 x 10^6 CD34+ cells/kg. After completion of stem cell collection, patients receive dasatinib PO twice daily until 3 days before transplantation.

TRANSPLANTATION: Beginning >= 4 weeks after recovery from toxicity related to previous treatment, patients receive melphalan IV over 30 minutes on days -2 and -1. Patients undergo autologous PBSCT on day 0. Patients then receive filgrastim SC beginning on day 0 and continuing until count recovery.

MAINTENANCE THERAPY: Beginning on day 30, patients receive dasatinib PO once daily. Treatment continues for >= 12 months in the absence of disease progression.

ALTERNATIVE CHEMOTHERAPY: Beginning 3-10 days after completion of CNS prophylaxis therapy, patients receive etoposide phosphate IV continuously on days 1-4, high-dose cytarabine IV over 2 hours every 12 hours for a total of 8 doses on days 1-4, and filgrastim SC once or twice daily beginning on day 14 and continuing until count recovery.

MAINTENANCE THERAPY: Patients receive dasatinib PO once daily beginning on day 30. Patients also receive vincristine sulfate IV every 4 weeks, dexamethasone for 5 days every 4 weeks, mercaptopurine PO once daily, and methotrexate PO once weekly. Treatment continues for >= 12 months in the absence of disease progression.

NOTE: Patients with CNS leukemia or testicular disease may receive additional treatment.

After completion of study treatment, patients are followed up every month for 1 year, every 3 months for 2 years, every 6 months for 2 years, and every year for 5 years.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Institute Palo Alto
  • Colorado
    • Aurora, Colorado, United States, 80012
      • The Medical Center of Aurora
    • Boulder, Colorado, United States, 80301
      • Boulder Community Hospital
    • Boulder, Colorado, United States, 80304
      • Rocky Mountain Cancer Centers-Boulder
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Colorado Springs, Colorado, United States, 80907
      • Rocky Mountain Cancer Centers-Penrose
    • Denver, Colorado, United States, 80210
      • Porter Adventist Hospital
    • Denver, Colorado, United States, 80218
      • Presbyterian - Saint Lukes Medical Center - Health One
    • Denver, Colorado, United States, 80218
      • SCL Health Saint Joseph Hospital
    • Denver, Colorado, United States, 80220
      • Rose Medical Center
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers-Midtown
    • Denver, Colorado, United States, 80220
      • Rocky Mountain Cancer Centers-Rose
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
    • Denver, Colorado, United States, 80222
      • Western States Cancer Research NCORP
    • Durango, Colorado, United States, 81301
      • Mercy Medical Center
    • Englewood, Colorado, United States, 80113
      • Mountain Blue Cancer Care Center - Swedish
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
    • Golden, Colorado, United States, 80401
      • Mountain Blue Cancer Care Center
    • Greeley, Colorado, United States, 80631
      • North Colorado Medical Center
    • Greenwood Village, Colorado, United States, 80111
      • Rocky Mountain Cancer Centers-Greenwood Village
    • Lakewood, Colorado, United States, 80228
      • Saint Anthony Hospital
    • Lakewood, Colorado, United States, 80228
      • Rocky Mountain Cancer Centers-Lakewood
    • Littleton, Colorado, United States, 80122
      • Littleton Adventist Hospital
    • Lone Tree, Colorado, United States, 80124
      • Sky Ridge Medical Center
    • Lone Tree, Colorado, United States, 80124
      • Rocky Mountain Cancer Centers-Sky Ridge
    • Longmont, Colorado, United States, 80501
      • Longmont United Hospital
    • Longmont, Colorado, United States, 80501
      • Rocky Mountain Cancer Centers-Longmont
    • Loveland, Colorado, United States, 80539
      • McKee Medical Center
    • Parker, Colorado, United States, 80138
      • Parker Adventist Hospital
    • Parker, Colorado, United States, 80138
      • Rocky Mountain Cancer Centers-Parker
    • Pueblo, Colorado, United States, 81004
      • Saint Mary Corwin Medical Center
    • Pueblo, Colorado, United States, 81008
      • Rocky Mountain Cancer Centers - Pueblo
    • Wheat Ridge, Colorado, United States, 80033
      • SCL Health Lutheran Medical Center
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19713
      • Helen F Graham Cancer Center
    • Newark, Delaware, United States, 19713
      • Delaware Clinical and Laboratory Physicians PA
    • Newark, Delaware, United States, 19713
      • Medical Oncology Hematology Consultants PA
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
    • Newark, Delaware, United States, 19713
      • Christiana Gynecologic Oncology LLC
    • Rehoboth Beach, Delaware, United States, 19971
      • Beebe Health Campus
    • Seaford, Delaware, United States, 19973
      • TidalHealth Nanticoke / Allen Cancer Center
    • Wilmington, Delaware, United States, 19801
      • Christiana Care Health System-Wilmington Hospital
  • Florida
    • Orlando, Florida, United States, 32803
      • AdventHealth Orlando
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60612
      • University of Illinois
    • Chicago, Illinois, United States, 60611
      • Hematology and Oncology Associates
    • Kankakee, Illinois, United States, 60901
      • Presence Saint Mary's Hospital
    • Libertyville, Illinois, United States, 60048
      • AMG Libertyville - Oncology
    • Niles, Illinois, United States, 60714
      • Illinois Cancer Specialists-Niles
    • Rockford, Illinois, United States, 61114
      • SwedishAmerican Regional Cancer Center/ACT
    • Skokie, Illinois, United States, 60076
      • Hematology Oncology Associates of Illinois - Skokie
  • Indiana
    • Fort Wayne, Indiana, United States, 46845
      • Fort Wayne Medical Oncology and Hematology Inc-Parkview
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas - El Dorado
    • Fort Scott, Kansas, United States, 66701
      • Cancer Center of Kansas - Fort Scott
    • Independence, Kansas, United States, 67301
      • Cancer Center of Kansas-Independence
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas-Kingman
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Liberal, Kansas, United States, 67905
      • Cancer Center of Kansas-Liberal
    • Manhattan, Kansas, United States, 66502
      • Cancer Center of Kansas-Manhattan
    • McPherson, Kansas, United States, 67460
      • Cancer Center of Kansas - McPherson
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas - Newton
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas - Pratt
    • Salina, Kansas, United States, 67401
      • Cancer Center of Kansas - Salina
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas - Wellington
    • Wichita, Kansas, United States, 67214
      • Ascension Via Christi Hospitals Wichita
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas-Wichita Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Wichita
    • Wichita, Kansas, United States, 67208
      • Associates In Womens Health
    • Wichita, Kansas, United States, 67214
      • Wichita NCI Community Oncology Research Program
    • Wichita, Kansas, United States, 67214
      • Wesley Medical Center
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas - Winfield
  • Maine
    • Augusta, Maine, United States, 04330
      • Harold Alfond Center for Cancer Care
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center
  • Maryland
    • Elkton, Maryland, United States, 21921
      • Christiana Care - Union Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Cancer Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Lake Success, New York, United States, 11042
      • Northwell Health NCORP
    • Lake Success, New York, United States, 11042
      • Northwell Health/Center for Advanced Medicine
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • New Hyde Park, New York, United States, 11040
      • Long Island Jewish Medical Center
    • New York, New York, United States, 10065
      • NYP/Weill Cornell Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • The Jewish Hospital
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Milton S Hershey Medical Center
  • Vermont
    • Burlington, Vermont, United States, 05405
      • University of Vermont and State Agricultural College
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
  • Wyoming
    • Cheyenne, Wyoming, United States, 82001
      • Cheyenne Regional Medical Center-West

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Unequivocal histologic diagnosis of ALL
• Detection of the t(9;22)(q34;q11) or 3-way variant by metaphase cytogenetics or BCR-ABL positive status by molecular analysis (Q-PCR or fluorescent in situ hybridization [FISH]) in a Cruise Lines International Association (CLIA)-approved laboratory
• No prior therapy except up to one week of corticosteroids and/or hydroxyurea to enable time for the detection of t(9;22)(q34;q11) or BCR/ABL
• Non-pregnant and non-nursing; treatment under this protocol would expose an unborn child to significant risks; women and men of reproductive potential should agree to use an effective means of birth control and contraception should continue for three months after the last dose of dasatinib to allow complete clearance of drug and its principal metabolites from the body; in women of childbearing potential, a pregnancy test will be required at study entry
• Left ventricular ejection fraction >= lower limit of institutional normal
• No myocardial infarction within 6 months
• No ventricular tachyarrhythmia within 6 months
• No major conduction abnormality (unless a cardiac pacemaker is present)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (chemotherapy, transplant); See Detailed Description

Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Drug: Cytarabine; Given IV; Other Names: .beta.-Cytosine arabinoside; 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-.beta.-D-Arabinofuranosylcytosine; 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-Beta-D-arabinofuranosylcytosine; 1.beta.-D-Arabinofuranosylcytosine; 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-; 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-; Alexan; Ara-C; ARA-cell; Arabine; Arabinofuranosylcytosine; Arabinosylcytosine; Aracytidine; Aracytin; Aracytine; Beta-Cytosine Arabinoside; CHX-3311; Cytarabinum; Cytarbel; Cytosar; Cytosine Arabinoside; Cytosine-.beta.-arabinoside; Cytosine-beta-arabinoside; Erpalfa; Starasid; Tarabine PFS; U 19920; U-19920; Udicil; WR-28453; Drug: Daunorubicin Hydrochloride; Given IV; Other Names: Cerubidin; Cerubidine; Cloridrato de Daunorubicina; Daunoblastin; Daunoblastina; Daunoblastine; Daunomycin Hydrochloride; Daunomycin, hydrochloride; Daunorubicin.HCl; Daunorubicini Hydrochloridum; FI-6339; Ondena; RP-13057; Rubidomycin Hydrochloride; Rubilem; Drug: Dasatinib; Given PO; Other Names: BMS-354825; Dasatinib Hydrate; Dasatinib Monohydrate; Sprycel; Drug: Cyclophosphamide; Given IV; Other Names: Cytoxan; CTX; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamide Monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; Drug: Mercaptopurine; Given PO; Other Names: 6-MP; Purinethol; 3H-Purine-6-thiol; 6 MP; 6 Thiohypoxanthine; 6 Thiopurine; 6-Mercaptopurine; 6-Mercaptopurine Monohydrate; 6-Purinethiol; 6-Thiopurine; 6-Thioxopurine; 6H-Purine-6-thione, 1,7-dihydro- (9CI); 7-Mercapto-1,3,4,6-tetrazaindene; Alti-Mercaptopurine; Azathiopurine; Bw 57-323H; Flocofil; Ismipur; Leukerin; Leupurin; Mercaleukim; Mercaleukin; Mercaptina; Mercaptopurinum; Mercapurin; Mern; NCI-C04886; Puri-Nethol; Purimethol; Purine, 6-mercapto-; Purine-6-thiol (8CI); Purine-6-thiol, monohydrate; Purinethiol; U-4748; WR-2785; Drug: Vincristine Sulfate; Given IV; Other Names: Oncovin; Kyocristine; Leurocristine Sulfate; Leurocristine, sulfate; Vincasar; Vincosid; Vincrex; Vincristine, sulfate; Biological: Pegfilgrastim; Given SC; Other Names: Filgrastim SD-01; filgrastim-SD/01; Fulphila; HSP-130; Jinyouli; Neulasta; Neulastim; Nyvepria; PEG-filgrastim; Pegcyte; Pegfilgrastim Biosimilar HSP-130; Pegfilgrastim Biosimilar Nyvepria; Pegfilgrastim Biosimilar Pegcyte; Pegfilgrastim Biosimilar PF-06881894; Pegfilgrastim Biosimilar Udenyca; Pegfilgrastim Biosimilar Ziextenzo; pegfilgrastim-apgf; pegfilgrastim-bmez; pegfilgrastim-cbqv; Pegfilgrastim-jmdb; PF-06881894; SD-01; SD-01 sustained duration G-CSF; Udenyca; Ziextenzo; Drug: Dexamethasone; Given PO or IV; Other Names: Decadron; Hemady; Aacidexam; Adexone; Aknichthol Dexa; Alba-Dex; Alin; Alin Depot; Alin Oftalmico; Amplidermis; Anemul mono; Auricularum; Auxiloson; Baycadron; Baycuten; Baycuten N; Cortidexason; Cortisumman; Decacort; Decadrol; Decadron DP; Decalix; Decameth; Decasone R.p.; Dectancyl; Dekacort; Deltafluorene; Deronil; Desamethasone; Desameton; Dexa-Mamallet; Dexa-Rhinosan; Dexa-Scheroson; Dexa-sine; Dexacortal; Dexacortin; Dexafarma; Dexafluorene; Dexalocal; Dexamecortin; Dexameth; Dexamethasone Intensol; Dexamethasonum; Dexamonozon; Dexapos; Dexinoral; Dexone; Dinormon; Dxevo; Fluorodelta; Fortecortin; Gammacorten; Hexadecadrol; Hexadrol; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; TaperDex; Visumetazone; ZoDex; Drug: Leucovorin Calcium; Given IV or PO; Other Names: Wellcovorin; folinic acid; Adinepar; Calcifolin; Calcium (6S)-Folinate; Calcium Folinate; Calcium Leucovorin; Calfolex; Calinat; Cehafolin; Citofolin; Citrec; Citrovorum Factor; Cromatonbic Folinico; Dalisol; Disintox; Divical; Ecofol; Emovis; Factor, Citrovorum; Flynoken A; Folaren; Folaxin; FOLI-cell; Foliben; Folidan; Folidar; Folinac; Folinate Calcium; Folinic Acid Calcium Salt Pentahydrate; Folinoral; Folinvit; Foliplus; Folix; Imo; Lederfolat; Lederfolin; Leucosar; leucovorin; Rescufolin; Rescuvolin; Tonofolin; Drug: Etoposide Phosphate; Given IV; Other Names: Etopophos; Biological: Filgrastim; Given SC; Other Names: G-CSF; r-metHuG-CSF; Neupogen; Filgrastim-aafi; Nivestym; Recombinant Methionyl Human Granulocyte Colony Stimulating Factor; rG-CSF; Tevagrastim; Drug: Melphalan; Given IV; Other Names: CB-3025; L-PAM; L-Sarcolysin; Alanine Nitrogen Mustard; L-Phenylalanine Mustard; L-Sarcolysin Phenylalanine mustard; L-Sarcolysine; Melphalanum; Phenylalanine Mustard; Phenylalanine Nitrogen Mustard; Sarcoclorin; Sarkolysin; WR-19813; Drug: Fludarabine Phosphate; Given IV; Other Names: 2-F-ara-AMP; Beneflur; Fludara; 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-; SH T 586; Drug: Tacrolimus; Given IV or PO; Other Names: Prograf; Hecoria; FK 506; Fujimycin; Protopic; Biological: Alemtuzumab; Given IV; Other Names: Campath; Campath-1H; Lemtrada; Monoclonal Antibody Campath-1H; MabCampath; Anti-CD52 Monoclonal Antibody; LDP-03; Drug: Methotrexate; Given IT, IV, or PO; Other Names: Abitrexate; Folex; Mexate; MTX; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex PFS; Lantarel; Ledertrexate; Lumexon; Maxtrex; Medsatrexate; Metex; Methoblastin; Methotrexate LPF; Methotrexate Methylaminopterin; Methotrexatum; Metotrexato; Metrotex; Mexate-AQ; Novatrex; Rheumatrex; Texate; Tremetex; Trexeron; Trixilem; WR-19039; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Undergo peripheral blood allogeneic HCT; Other Names: Allogeneic; Allogeneic Hematopoietic Cell Transplantation; Allogeneic Stem Cell Transplantation; HSC; HSCT; Stem Cell Transplantation, Allogeneic; Procedure: Autologous Hematopoietic Stem Cell Transplantation; Undergo peripheral blood autologous HCT; Other Names: Autologous Stem Cell Transplantation; AHSCT; Autologous; Autologous Hematopoietic Cell Transplantation; Autologous Stem Cell Transplant; Stem Cell Transplantation, Autologous; Procedure: In Vitro-Treated Peripheral Blood Stem Cell Transplantation; Undergo peripheral blood autologous or allogeneic HCT; Other Names: in vitro-treated PBPC transplantation; in vitro-treated peripheral blood progenitor cell transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival Defined From the Date of First Induction Complete Response (CR) to Relapse or Death Due to Any Cause	Estimated using the Kaplan-Meier estimator. Proportions will be estimated using point as well as interval estimators. All interval estimators will be constructed using the finite sample size sampling distribution at the unadjusted two-sided level of 0.05.	At 3 years after CR

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Probability of Being BCR-ABL Negative in the Bone Marrow and Peripheral Blood at the Completion of the CNS Prophylaxis Course (Restricted to Those Patients Achieving a CR)	Proportions will be estimated based on the combined and individual cohorts.	10 years
Feasibility of Maintenance Therapy in This Patient Population (Restricted to Those Patients Achieving a CR). Feasibility Will be Defined as the Number of Deaths Ocuring.	Proportions will be estimated based on the combined and individual cohorts.	10 years
Overall Survival (OS)	Estimated using the Kaplan-Meier estimator. Proportions will be estimated using point as well as interval estimators. All interval estimators will be constructed using the finite sample size sampling distribution at the unadjusted two-sided level of 0.05.	10 years
Disease Free Survival (DFS)	Estimated using the Kaplan-Meier estimator. Proportions will be estimated using point as well as interval estimators. All interval estimators will be constructed using the finite sample size sampling distribution at the unadjusted two-sided level of 0.05.	10 years
Response	Proportion of patients reaching a CR. A CR requires the following: an absolute neutrophil count (segs and bands) >1000/μL, no circulating blasts, platelets >100,000/μL; adequate bone marrow cellularity with trilineage hematopoiesis, and <5% marrow leukemia blast cells. All previous extramedullary manifestations of disease must be absent (e.g., lymphadenopathy, splenomegaly, skin or gum infiltration, testicular masses, or CNS involvement).	10 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Matthew J Wieduwilt, Alliance for Clinical Trials in Oncology

Publications and helpful links

General Publications

• Wieduwilt MJ, Yin J, Wetzler M, Uy GL, Powell BL, Kolitz JE, Liedtke M, Stock W, Beumer JH, Mattison RJ, Storrick E, Christner SM, Lewis LD, Devine S, Stone RM, Larson RA. Dasatinib and dexamethasone followed by hematopoietic cell transplantation for adults with Ph-positive ALL. Blood Adv. 2021 Nov 23;5(22):4691-4700. doi: 10.1182/bloodadvances.2021004813.

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2010
• Primary Completion (Actual): November 14, 2017
• Study Completion (Actual): November 15, 2021

Study Registration Dates

• First Submitted: December 7, 2010
• First Submitted That Met QC Criteria: December 7, 2010
• First Posted (Estimate): December 8, 2010

Study Record Updates

• Last Update Posted (Actual): April 4, 2023
• Last Update Submitted That Met QC Criteria: March 7, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Protective Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Micronutrients; Protein Kinase Inhibitors; Adjuvants, Immunologic; Antibiotics, Antineoplastic; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Antidotes; Vitamin B Complex; Hematinics; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Calcineurin Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101; Cyclophosphamide; Etoposide; Etoposide phosphate; Antibodies; Immunoglobulins; Leucovorin; Calcium; Levoleucovorin; Lenograstim; Melphalan; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Fludarabine; Fludarabine phosphate; Cytarabine; Methotrexate; Vincristine; Daunorubicin; Mercaptopurine; Folic Acid; Calcium, Dietary; Tacrolimus; Dasatinib; Alemtuzumab; Mechlorethamine; Nitrogen Mustard Compounds
• Other Study ID Numbers: NCI-2011-02621 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180821 (U.S. NIH Grant/Contract); U10CA031946 (U.S. NIH Grant/Contract); CALGB 10701/CTSU C10701; CDR0000690286; CALGB-10701 (Other Identifier: CTEP)